Organocatalytic chiral Bronsted acid

Next, another work on a Br0nsted acid-catalyzed intramolecular electrocyclization reaction was reported by list [36]. They demonstrated that chiral Bronsted acid 104 could efficiently promote the cycloisomerization of a,P-unsaturated hydrazones 105 to give pyrazoUnes 106 in high yields and with good enantioselectivity (Scheme 36.28). This is also the first example of an organocatalytic asymmetric 671 electrocyclization reaction. 

The enantioselective organocatalytic functionaUzation of carbonyl compounds at the 7 position represents a highly challenging and persistent problem for asymmetric synthesis [33]. Recently, Melchiorre and coworkers [34] reported a chiral Bronsted acid-assisted dienamine catalysis for the direct asymmetric y-alkylation of a-substituted linear a,(l-unsaturated aldehydes (Scheme 43.22). In this reaction, the chiral phosphoric acid 106 can induce the formation of a chiral contact ion-pair from alcohol 103 [35], which may synergistically engage in a matched combination with the chiral covalent dienamine intermediate derived from chiral primary... 

Considerable effort has been devoted to the development of enantiocatalytic MBH reactions, either with purely organic catalysts, or with metal complexes. Paradoxically, metal complex-mediated reactions were usually found to be more efficient in terms of enantioselectivity, reaction rates and scope of the substrates, than their organocatalytic counterparts [36, 56]. However, this picture is actually changing, and during the past few years the considerable advances made in organocatalytic MBH reactions have allowed the use of viable alternatives to the metal complex-mediated reactions. Today, most of the organocatalysts developed are bifunctional catalysts in which the chiral N- and P-based Lewis base is tethered with a Bronsted acid, such as (thio)urea and phenol derivatives. Alternatively, these acid co-catalysts can be used as additives with the nucleophile base. 

Asymmetric organocatalytic Morita-Baylis-Hillman reactions offer synthetically viable alternatives to metal-complex-mediated reactions. The reaction is best mediated with a combination of nucleophilic tertiary amine/phosphine catalysts, and mild Bronsted acid co-catalysts usually, bifunctional chiral catalysts having both nucleophilic Lewis base and Bronsted acid site were seen to be the most efficient. Although many important factors governing the reactions were identified, our present understanding of the basic factors, and the control of reactivity and selectivity remains incomplete. Whilst substrate dependency is still considered to be an important issue, an increasing number of transformations are reaching the standards of current asymmetric reactions. 

Over the past decade, rapid growth has been achieved in organocatalytic asymmetric Diels-Alder and hetero-Diels-Alder reactions. Numerous organocatalysts such as chiral amines, guanidines, N-heterocyclic carbenes, Bronsted acids, and bifunctional catalysts have been successfully developed. The activation modes for these catalysts, such as imine-catalysis, enamine-catalysis, dienamine catalysis. 

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